Transcriptomic profiling of trophoblast fusion using BeWo and JEG-3 cell lines.

In human placenta, alteration in trophoblast differentiation has a major impact on placental maintenance and integrity. However, little is known about the mechanisms that control cytotrophoblast fusion. The BeWo cell line is used to study placental function, since it forms syncytium and secretes hormones after treatment with cAMP or forskolin. In contrast, the JEG-3 cell line fails to undergo substantial fusion. Therefore, BeWo and JEG-3 cells were used to identify a set of genes responsible for trophoblast fusion. Cells were treated with forskolin for 48 h to induce fusion. RNA was extracted, hybridised to Affymetrix HuGene ST1.0 arrays and analysed using system biology. Trophoblast differentiation was evaluated by real-time PCR and immunocytochemistry analysis. Moreover, some of the identified genes were validated by real-time PCR and their functional capacity was demonstrated by western blot using phospho-specific antibodies and CRISPR/cas9 knockdown experiments. Our results identified a list of 32 altered genes in fused BeWo cells compared to JEG-3 cells after forskolin treatment. Among these genes, four were validated by RT-PCR, including salt-inducible kinase 1 (SIK1) gene which is specifically upregulated in BeWo cells upon fusion and activated after 2 min with forskolin. Moreover, silencing of SIK1 completely abolished the fusion. Finally, SIK1 was shown to be at the center of many biological and functional processes, suggesting that it might play a role in trophoblast differentiation. In conclusion, this study identified new target genes implicated in trophoblast fusion. More studies are required to investigate the role of these genes in some placental pathology.

Autoantibodies in traumatic brain injury and central nervous system trauma.

Despite the debilitating consequences and the widespread prevalence of brain trauma insults including spinal cord injury (SCI) and traumatic brain injury (TBI), there are currently few effective therapies for most of brain trauma sequelae. As a consequence, there has been a major quest for identifying better diagnostic tools, predictive models, and directed neurotherapeutic strategies in assessing brain trauma. Among the hallmark features of brain injury pathology is the central nervous systems' (CNS) abnormal activation of the immune response post-injury. Of interest, is the occurrence of autoantibodies which are produced following CNS trauma-induced disruption of the blood-brain barrier (BBB) and released into peripheral circulation mounted against self-brain-specific proteins acting as autoantigens. Recently, autoantibodies have been proposed as the new generation class of biomarkers due to their long-term presence in serum compared to their counterpart antigens. The diagnostic and prognostic value of several existing autoantibodies is currently being actively studied. Furthermore, the degree of direct and latent contribution of autoantibodies to CNS insult is still not fully characterized. It is being suggested that there may be an analogy of CNS autoantibodies secretion with the pathophysiology of autoimmune diseases, in which case, understanding and defining the role of autoantibodies in brain injury paradigm (SCI and TBI) may provide a realistic prospect for the development of effective neurotherapy. In this work, we will discuss the accumulating evidence about the appearance of autoantibodies following brain injury insults. Furthermore, we will provide perspectives on their potential roles as pathological components and as candidate markers for detecting and assessing CNS injury.

An updated overview of animal models in neuropsychiatry.

Animal models are vital tools to study the genetic, molecular, cellular, and environmental parameters involved in several neuropsychiatric disorders. Over the years, these models have expanded our understanding of the pathogenesis of many neuropsychiatric disorders and neurodegenerative diseases. Although animal models have been widely used in psychiatry, and despite several years of extensive research with these models, their validity is still being investigated and presents a challenge to both investigators and clinicians as well. In this concise review, we will describe the most common animal models utilized in neuropsychiatry, including animal models of depression, anxiety, and psychosis. In addition, we will also discuss the validity and reliability of these models and current challenges in this domain. Furthermore, this work will discuss the role of gene-environment interaction as an additional contributing factor that modulates neuropsychological outcome and its implication on animal models. This overview will give a succinct summary of animal models in psychiatry which will be useful both to the seasoned researcher, as well as novices in the field.